Department of Chemical and Biomolecular Engineering, University of California, Berkeley, CA, USA.
Department of Chemical and Biomolecular Engineering, University of California, Berkeley, CA, USA; Department of Bioengineering, University of California, Berkeley, CA, USA; The Helen Wills Neuroscience Institute, University of California, Berkeley, CA, USA; Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
Curr Opin Neurobiol. 2018 Jun;50:163-170. doi: 10.1016/j.conb.2017.12.011. Epub 2018 Mar 31.
Optimization of traditional replication-competent viral tracers has granted access to immediate synaptic partners of target neuronal populations, enabling the dissection of complex brain circuits into functional neural pathways. The excessive virulence of most conventional tracers, however, impedes their utility in revealing and genetically perturbing cellular function on long time scales. As a promising alternative, the natural capacity of adeno-associated viral (AAV) vectors to safely mediate persistent and robust gene expression has stimulated strong interest in adapting them for sparse neuronal labeling and physiological studies. Furthermore, increasingly refined engineering strategies have yielded novel AAV variants with enhanced target specificity, transduction, and retrograde trafficking in the CNS. These potent vectors offer new opportunities for characterizing the identity and connectivity of single neurons within immense networks and modulating their activity via robust delivery of functional genetic tools.
优化传统复制型病毒示踪剂使我们能够直接追踪目标神经元群体的突触伙伴，从而将复杂的大脑回路分解为功能性神经通路。然而，大多数传统示踪剂的过度毒性阻碍了它们在长时间尺度上揭示和遗传干扰细胞功能的应用。腺相关病毒（AAV）载体安全介导持续和强大基因表达的自然能力是一种很有前途的替代方法，这激发了人们强烈的兴趣，希望将其用于稀疏神经元标记和生理研究。此外，日益精细的工程策略产生了新型 AAV 变体，这些变体在中枢神经系统中具有增强的靶向特异性、转导和逆行转运能力。这些有效的载体为在巨大的网络中描述单个神经元的身份和连接性，并通过强大的功能遗传工具的传递来调节它们的活性提供了新的机会。
